Abstract
Herein, we report the discovery of a novel potent, selective, CNS penetrant, and orally bioavailable mGlu 4 PAM, VU0652957 (VU2957, Valiglurax). VU2957 possessed attractive in vitro and in vivo pharmacological and DMPK properties across species. To advance toward the clinic, a spray-dried dispersion (SDD) formulation of VU2957 was developed to support IND-enabling toxicology studies. Based on its overall profile, VU2957 was evaluated as a preclinical development candidate for the treatment of Parkinson's disease.
| Original language | English |
|---|---|
| Pages (from-to) | 255-260 |
| Number of pages | 6 |
| Journal | ACS Medicinal Chemistry Letters |
| Volume | 10 |
| Issue number | 3 |
| DOIs | |
| State | Published - 14 Mar 2019 |
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Keywords
- Parkinson's disease
- Positive allosteric modulator (PAM)
- VU2957
- metabotropic glutamate receptor 4 (mGlu )
Cite this
}
Discovery of VU2957 (Valiglurax) : An mGlu 4 Positive Allosteric Modulator Evaluated as a Preclinical Candidate for the Treatment of Parkinson's Disease. / Panarese, Joseph D.; Engers, Darren W.; Wu, Yong Jin; Bronson, Joanne J.; Macor, John E.; Chun, Aspen; Rodriguez, Alice L.; Felts, Andrew S.; Engers, Julie L.; Loch, Matthew T.; Emmitte, Kyle Allen; Castelhano, Arlindo L.; Kates, Michael J.; Nader, Michael A.; Jones, Carrie K.; Blobaum, Anna L.; Conn, P. Jeffrey; Niswender, Colleen M.; Hopkins, Corey R.; Lindsley, Craig W.
In: ACS Medicinal Chemistry Letters, Vol. 10, No. 3, 14.03.2019, p. 255-260.Research output: Contribution to journal › Article
TY - JOUR
T1 - Discovery of VU2957 (Valiglurax)
T2 - An mGlu 4 Positive Allosteric Modulator Evaluated as a Preclinical Candidate for the Treatment of Parkinson's Disease
AU - Panarese, Joseph D.
AU - Engers, Darren W.
AU - Wu, Yong Jin
AU - Bronson, Joanne J.
AU - Macor, John E.
AU - Chun, Aspen
AU - Rodriguez, Alice L.
AU - Felts, Andrew S.
AU - Engers, Julie L.
AU - Loch, Matthew T.
AU - Emmitte, Kyle Allen
AU - Castelhano, Arlindo L.
AU - Kates, Michael J.
AU - Nader, Michael A.
AU - Jones, Carrie K.
AU - Blobaum, Anna L.
AU - Conn, P. Jeffrey
AU - Niswender, Colleen M.
AU - Hopkins, Corey R.
AU - Lindsley, Craig W.
PY - 2019/3/14
Y1 - 2019/3/14
N2 - Herein, we report the discovery of a novel potent, selective, CNS penetrant, and orally bioavailable mGlu 4 PAM, VU0652957 (VU2957, Valiglurax). VU2957 possessed attractive in vitro and in vivo pharmacological and DMPK properties across species. To advance toward the clinic, a spray-dried dispersion (SDD) formulation of VU2957 was developed to support IND-enabling toxicology studies. Based on its overall profile, VU2957 was evaluated as a preclinical development candidate for the treatment of Parkinson's disease.
AB - Herein, we report the discovery of a novel potent, selective, CNS penetrant, and orally bioavailable mGlu 4 PAM, VU0652957 (VU2957, Valiglurax). VU2957 possessed attractive in vitro and in vivo pharmacological and DMPK properties across species. To advance toward the clinic, a spray-dried dispersion (SDD) formulation of VU2957 was developed to support IND-enabling toxicology studies. Based on its overall profile, VU2957 was evaluated as a preclinical development candidate for the treatment of Parkinson's disease.
KW - Parkinson's disease
KW - Positive allosteric modulator (PAM)
KW - VU2957
KW - metabotropic glutamate receptor 4 (mGlu )
UR - http://www.scopus.com/inward/record.url?scp=85055174677&partnerID=8YFLogxK
U2 - 10.1021/acsmedchemlett.8b00426
DO - 10.1021/acsmedchemlett.8b00426
M3 - Article
AN - SCOPUS:85055174677
VL - 10
SP - 255
EP - 260
JO - ACS Medicinal Chemistry Letters
JF - ACS Medicinal Chemistry Letters
SN - 1948-5875
IS - 3
ER -